Abducens Nerve Palsy and Meningitis by Rickettsia typhi

Moy, Wai Lun; Ooi, Say Tat

doi:10.4269/ajtmh.14-0559

Cited by 21 publications

(15 citation statements)

References 35 publications

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“…In line with these findings, several cases of meningitis and encephalitis in R. typhi patients have been reported (92)(93)(94)(95)(96). In some cases, delayed or prolonged neurologic manifestations have been observed (92,94).…”

Section: Discussionsupporting

confidence: 60%

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

et al. 2016

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bRickettsioses are emerging febrile diseases caused by obligate intracellular bacteria belonging to the family Rickettsiaceae. Rickettsia typhi belongs to the typhus group (TG) of this family and is the causative agent of endemic typhus, a disease that can be fatal. In the present study, we analyzed the course of R. typhi infection in C57BL/6 RAG1 ؊/؊ mice. Although these mice lack adaptive immunity, they developed only mild and temporary symptoms of disease and survived R. typhi infection for a long period of time. To our surprise, 3 to 4 months after infection, C57BL/6 RAG1 ؊/؊ mice suddenly developed lethal neurological disorders. Analysis of these mice at the time of death revealed high bacterial loads, predominantly in the brain. This was accompanied by a massive expansion of microglia and by neuronal cell death. Furthermore, high numbers of infiltrating CD11b ؉ macrophages were detectable in the brain. In contrast to the microglia, these cells harbored R. typhi and showed an inflammatory phenotype, as indicated by inducible nitric oxide synthase (iNOS) expression, which was not observed in the periphery. Having shown that R. typhi persists in immunocompromised mice, we finally asked whether the bacteria are also able to persist in resistant C57BL/6 and BALB/c wild-type mice. Indeed, R. typhi could be recultivated from lung, spleen, and brain tissues from both strains even up to 1 year after infection. This is the first report demonstrating persistence and reappearance of R. typhi, mainly restricted to the central nervous system in immunocompromised mice.

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Section: Discussionsupporting

confidence: 60%

Persisting Rickettsia typhi Causes Fatal Central Nervous System Inflammation

et al. 2016

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“…Murine typhus, caused by the obligate intracellular organism Rickettsia typhi is a disease transmitted to humans by the rat flea, Xenopsylla cheopis [1] and is a common cause of acute fever in Southeast Asia [2e4]. The disease has worldwide distribution but its true incidence is difficult to determine because cases are often underdiagnosed or misdiagnosed because of its non-specific clinical manifestations, usually self-limiting nature and lack of accessible diagnostic tests [1,5].…”

Section: Introductionmentioning

confidence: 99%

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients

Phakhounthong

Mukaka

Dittrich

et al. 2020

Clinical Microbiology and Infection

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Objectives: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cutoffs ; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cutoff parameters for indirect immunofluorescence assay (IFA). Methods: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. Results: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to 3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36e204 days) and IgG was 177 days (interquartile range 134e355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cutoff reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%e85.2% sensitivity; 89.9%, 95% CI 62.5%e100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%e87.6% sensitivity; 99%, 95% CI 95%e100% specificity). Conclusions: This study suggests suitable diagnostic cutoffs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cutoffs in other geographically diverse locations.

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“…Murine typhus has protean manifestations. Illness can range from an undifferentiated febrile syndrome to life threatening illness causing pneumonia, respiratory failure, acute renal failure, acute hepatitis, meningitis or meningoencephalitis, cranial nerve palsies, coagulopathy, disseminated intravascular coagulation (DIC) and death (Simon et al, 2011;Moy and Ooi, 2015;X-ray, 2010). Neurological manifestations have been described both in children (Galanakis et al, 2002) and in adults.…”

Section: Discussionmentioning

confidence: 99%

“…Papilledema, cranial nerve palsies, focal neurologic deficits and seizures have been reported (Moy and Ooi 2015;Simon et al, 2011). Meningoencephalitis, behavior and memory disturbances as delayed consequences have been published, although recovery occurs (Silpapojakul et al, 1991;Masalha et al, 1998;Moy and Ooi, 2015;Simon et al, 2011;Massung et al, 2001;Dittrich et al, 2015;Samra et al, 1989;Carr et al, 2014). Status epilepticus has been described in Japanese spotted fever, which is caused by Rickettsia japonica (Nakata et al, 2012) as well as in MT with fatality (Stephens et al, 2018).…”

Section: Discussionmentioning

confidence: 99%